Disuse Muscle Atrophy Research Articles

Temporal Muscle-specific Disuse Atrophy during One Week of Leg Immobilization.

Musculoskeletal injuries necessitate periods of disuse (i.e., limb immobilization) during which rapid skeletal muscle atrophy occurs. The relative susceptibility of different muscles of the thigh to disuse atrophy remains uninvestigated. We assessed muscle disuse atrophy of individual thigh muscles throughout 1 wk of unilateral knee immobilization. Thirteen healthy, young (20.2 ± 0.6 yr) men underwent 7 d of unilateral leg immobilization via knee bracing. Magnetic resonance imaging scans were performed bilaterally prior to, and following 2 and 7 d of immobilization to determine the volume and anatomical cross-sectional area of the individual muscle groups of the upper legs. In contrast to the control leg, total thigh muscle volume had decreased by 1.7% ± 0.3% (P < 0.01) and 5.5% ± 0.6% (P < 0.001) in the immobilized leg after 2 and 7 d of disuse, respectively. Muscle loss was significantly greater in the Musculus quadriceps (day 2; 1.7% ± 0.3% (P < 0.05) and day 7; 6.7% ± 0.6%) when compared with the Musculus hamstrings (day 2; 1.4% ± 0.2% (P < 0.01) and day 7; 3.5% ± 0.3%) after 7 d of disuse (P < 0.001). Individual muscles of the thigh exhibited different atrophy rates with the Musculus vastus lateralis anatomical cross-sectional area showing the greater (2.6% ± 0.4% and 7.2% ± 0.8%), and the Musculus gracilis the lesser (1.1% ± 0.7% and 2.3% ± 1.0%) decline following 2 and 7 d of immobilization, respectively (P < 0.01). Thigh muscle disuse atrophy occurs rapidly and is already evident within 2 d of leg immobilization and progresses at a similar rate over the next 5 d (~0.8% muscle loss per day). M. quadriceps muscle shows more atrophy when compared with the M. hamstrings.

MicroRNAs facilitate skeletal muscle maintenance and metabolic suppression in hibernating brown bears.

Hibernating brown bears, Ursus arctos, undergo extended periods of inactivity and yet these large hibernators are resilient to muscle disuse atrophy. Physiological characteristics associated with atrophy resistance in bear muscle have been examined (e.g., muscle mechanics, neural activity) but roles for molecular signaling/regulatory mechanisms in the resistance to muscle wasting in bears still require investigation. Using quantitative reverse transcription PCR (RT-qPCR), the present study characterized the responses of 36 microRNAs linked with development, metabolism, and regeneration of skeletal muscle, in the vastus lateralis of brown bears comparing winter hibernating and summer active animals. Relative levels of mRNA of selected genes (mef2a, pax7, id2, prkaa1, and mstn) implicated upstream and downstream of the microRNAs were examined. Results indicated that hibernation elicited a myogenic microRNA, or "myomiR", response via MEF2A-mediated signaling. Upregulation of MEF2A-controlled miR-1 and miR-206 and respective downregulation of pax7 and id2 mRNA are suggestive of responses that promote skeletal muscle maintenance. Increased levels of metabolic microRNAs, such as miR-27, miR-29, and miR-33, may facilitate metabolic suppression during hibernation via mechanisms that decrease glucose uptake and fatty acid oxidation. This study identified myomiR-mediated mechanisms for the promotion of muscle regeneration, suppression of ubiquitin ligases, and resistance to muscle atrophy during hibernation mediated by observed increases in miR-206, miR-221, miR-31, miR-23a, and miR-29b. This was further supported by the downregulation of myomiRs associated with a muscle injury and inflammation (miR-199a and miR-223) during hibernation. The present study provides evidence of myomiR-mediated signaling pathways that are activated during hibernation to maintain skeletal muscle functionality in brown bears.

Cistanche tubulosa (Schenk) Wight Extract Enhances Hindlimb Performance and Attenuates Myosin Heavy Chain IId/IIx Expression in Cast-Immobilized Mice.

Skeletal muscle atrophy is encountered in many clinical conditions, but a pharmacological treatment has not yet been established. Cistanche tubulosa (Schenk) Wight is an herbal medicine used in traditional Japanese and Chinese medicine. In the current study, we investigated the effect of C. tubulosa extract (CTE) on atrophied muscle in vivo. We also investigated hindlimb cast immobilization in mice and devised a novel type of hindlimb-immobilizing cast, consisting of sponge-like tape and a thin plastic tube. Using this method, 3 out of 4 groups of mice (n = 11 for each group) were cast-immobilized in the hindlimbs and administered CTE or vehicle for 13 days. A sham procedure was performed in the mice of the fourth group to which the vehicle was administered. Next, the triceps surae muscles (TS) were excised. To analyze the effect of the novel cast system and CTE administration on muscle atrophy, we evaluated TS wet weight and myofiber cross-sectional area (CSA). We also determined MyHC IId/IIx expression levels by western blotting, since their increase is a hallmark of disuse muscle atrophy, suggesting slow-to-fast myofiber type shift. Moreover, we performed two tests of hindlimb performance. The novel cast immobilization method significantly reduced TS wet weight and myofiber CSA. This was accompanied by deterioration of hindlimb function and an increase in MyHC IId/IIx expression. CTE administration did not alter TS wet weight or myofiber CSA; however, it showed a trend of amelioration of the loss of hindlimb function and of suppression of the increased MyHC IId/IIx expression in cast-immobilized mice. Our novel hindlimb cast immobilization method effectively induced muscle atrophy. CTE did not affect muscle mass, but suppressed the shift from slow to fast myofiber type in cast-immobilized mice, ameliorating hindlimb function deterioration.

Elevated p70S6K phosphorylation in rat soleus muscle during the early stage of unloading: Causes and consequences

Currently, there is a lack of investigation into the initial signaling events underlying the development of disuse muscle atrophy. The study was aimed to (i) identify an assumed relationship between AMPK dephosphorylation and p70S6K hyperphosphorylation in the initial period of hindlimb unloading (HS), and (ii) assess the signaling consequences of p70S6K hyperphosphorylation following 24-h HS. For experiment 1, rats were treated with AMPK activator (AICAR) for 6 d before HS as well as during 24-h HS. For experiment 2, rats were treated with mTORC1 inhibitor rapamycin during 24-h HS. The key signaling markers implicated in protein turnover were assessed using WB and RT-PCR. One-day HS resulted in a significant upregulation of MuRF-1 and MAFbx expression, increase in p70S6K (Thr389) and IRS-1 (Ser639) phosphorylation and a significant decrease in phosphorylated AMPK, AKT, FOXO3, total IRS-1 content, and HDAC5 nuclear content. AMPK and p70S6K phosphorylation did not differ from control in AICAR-treated unloaded rats. Rapamycin treatment during unloading abolished p70S6K and E3 ligases upregulation and increased HDAC5 nuclear accumulation. The results of the study suggest that mTORC-1/p70S6K signaling pathway in rat soleus muscle is activated following 24-h mechanical unloading. This activation is facilitated by a decrease in AMPK phosphorylation. Increased p70S6K activity at the initial stage of hindlimb unloading could lead to the upregulation of E3 ligases MAFbx/atrogin-1 and MuRF-1 via nuclear export of HDAC5.

Oral glutamine supplementation attenuates inflammation and oxidative stress-mediated skeletal muscle protein content degradation in immobilized rats: Role of 70 kDa heat shock protein

Skeletal muscle disuse results in myofibrillar atrophy and protein degradation, via inflammatory and oxidative stress-mediated NF-kB signaling pathway activation. Nutritional interventions, such as l-glutamine (GLN) supplementation have shown antioxidant properties and cytoprotective effects through the modulation on the 70-kDa heat shock protein (HSP70) expression. However, these GLN-mediated effects on cell signaling pathways and biochemical mechanisms that control the myofibrillar protein content degradation in muscle disuse situations are poorly known yet. This study investigated the effects of oral GLN plus l-alanine (ALA; GLN ​+ ​ALA-solution) supplementation, either in their free or dipeptide (L-alanyl-l-glutamine-DIP) form, on GLN-glutathione (GSH) axis and cytoprotection mediated by HSP70 protein expression in the slow-twitch soleus and fast-twitch gastrocnemius skeletal muscle of rats submitted to 14-days of hindlimb immobilization-induced disuse muscle atrophy. Forty-eight Wistar rats were distributed into 6 groups: hindlimb immobilized (IMOB group) and hindlimb immobilized orally supplemented with either GLN (1 g kg−1) plus ALA (0.61 g kg−1) ​(GLN ​+ ​ALA-IMOB group) or 1.49 ​g ​kg−1 of DIP (DIP-IMOB group) and; no-immobilized (CTRL) and no-immobilized supplemented GLN ​+ ​ALA and DIP baselines groups. All animals, including CTRL and IMOB rats (water), were supplemented via intragastric gavage for 14 days, concomitantly to immobilization period. Plasma and muscle GLN levels, lipid (thiobarbituric acid reactive substances-TBARS) and protein (carbonyl) peroxidation, erythrocyte concentration of reduced GSH and GSH disulfide (GSSG), plasma and muscle pro-inflammatory TNF-α levels, muscle IKKα/β-NF-kB signaling pathway and, the myofibrillar protein content (MPC) were measured. The MPC was significantly lower in IMOB rats, compared to CTRL, GLN ​+ ​ALA, and DIP animals (p ​< ​0.05). This finding was associated with reduced plasma and muscle GLN concentration, equally in IMOB animals. Conversely, both GLN ​+ ​ALA and DIP supplementation restored plasma and muscle GLN levels, which equilibrated GSH and intracellular redox status (GSSG/GSH ratio) in erythrocytes and skeletal muscle even as, increased muscle HSP70 protein expression; attenuating oxidative stress and TNF-α-mediated NF-kB pathway activation, fact that reverberated on reduction of MPC degradation in GLN ​+ ​ALA-IMOB and DIP-IMOB animals (p ​< ​0.05). In conclusion, the findings shown herein support the oral GLN ​+ ​ALA and DIP supplementations as a therapeutic and effective nutritional alternative to attenuate the deleterious effects of the skeletal muscle protein degradation induced by muscle disuse.

High-Molecular-Weight Polyphenol-Rich Fraction of Black Tea Does Not Prevent Atrophy by Unloading, But Promotes Soleus Muscle Mass Recovery from Atrophy in Mice.

Previously, we reported that polyphenol-rich fraction (named E80) promotes skeletal muscle hypertrophy induced by functional overload in mice. This study indicates that E80 has potential for affecting skeletal muscle mass. Then, we evaluate the effect of E80 on atrophic and recovery conditions of skeletal muscle in mice. Hindlimb suspension (unloading) and relanding (reloading) are used extensively to observe disuse muscle atrophy and subsequent muscle mass recovery from atrophy. Eight-week old C57BL/6 mice were fed either a normal diet or a diet containing 0.5% E80 for two weeks under conditions of hindlimb suspension and a subsequent 5 or 10 days of reloading. We found that E80 administration did not prevent atrophy during hindlimb suspension, but promoted recovery of slow-twitch (soleus) muscle mass from atrophy induced by hindlimb suspension. After five days of reloading, we discovered that phosphorylation of the Akt/mammalian target of rapamycin (mTOR) pathway proteins, such as Akt and P70 ribosomal protein S6 kinase (S6K), was activated in the muscle. Therefore, E80 administration accelerated mTOR signal and increased protein synthesis in the reloaded soleus muscle.

OR26: Omega 3 Fatty Acid Supplementation Attenuates Muscle Disuse Atrophy During Two Weeks of Unilateral Leg Immobilization in Young Women

OR26: Omega 3 Fatty Acid Supplementation Attenuates Muscle Disuse Atrophy During Two Weeks of Unilateral Leg Immobilization in Young Women

Repetitive vascular occlusion stimulus (RVOS) versus standard care to prevent muscle wasting in critically ill patients (ROSProx):a study protocol for a pilot randomised controlled trial

BackgroundForty per cent of critically ill patients are affected by intensive care unit-acquired weakness (ICU-AW), to which skeletal muscle wasting makes a substantial contribution. This can impair outcomes in hospital, and can cause long-term physical disability after hospital discharge. No effective mitigating strategies have yet been identified.Application of a repetitive vascular occlusion stimulus (RVOS) a limb pressure cuff inducing brief repeated cycles of ischaemia and reperfusion, can limit disuse muscle atrophy in both healthy controls and bed-bound patients recovering from knee surgery. We wish to determine whether RVOS might be effective in mitigating against muscle wasting in the ICU. Given that RVOS can also improve vascular function in healthy controls, we also wish to assess such effects in the critically ill. We here describe a pilot study to assess whether RVOS application is safe, tolerable, feasible and acceptable for ICU patients.MethodsThis is a randomised interventional feasibility trial. Thirty-two ventilated adult ICU patients with multiorgan failure will be recruited within 48 h of admission and randomised to either the intervention arm or the control arm. Intervention participants will receive RVOS twice daily (except only once on day 1) for up to 10 days or until ICU discharge.Serious adverse events and tolerability (pain score) will be recorded; feasibility of trial procedures will be assessed against pre-specified criteria and acceptability by semi-structured interview. Together with vascular function, muscle mass and quality will be assessed using ultrasound and measures of physical function at baseline, on days 6 and 11 of study enrolment, and at ICU and hospital discharge. Blood and urine biomarkers of muscle metabolism, vascular function, inflammation and DNA damage/repair mechanism will also be analysed. The Health questionnaire will be completed 3 months after hospital discharge.DiscussionIf this study demonstrates feasibility, the derived data will be used to inform the design (and sample size) of an appropriately-powered prospective trial to clarify whether RVOS can help preserve muscle mass/improve vascular function in critically ill patients.Trial registrationISRCTN Registry, ISRCTN44340629. Registered on 26 October 2017.

A Novel Amino Acid Composition Ameliorates Short-Term Muscle Disuse Atrophy in Healthy Young Men.

Skeletal muscle disuse leads to atrophy, declines in muscle function, and metabolic dysfunction that are often slow to recover. Strategies to mitigate these effects would be clinically relevant. In a double-blind randomized-controlled pilot trial, we examined the safety and tolerability as well as the atrophy mitigating effect of a novel amino acid composition (AXA2678), during single limb immobilization. Twenty healthy young men were randomly assigned (10 per group) to receive AXA2678 or an excipient- and energy-matched non-amino acid containing placebo (PL) for 28d: days 1–7, pre-immobilization; days 8–15, immobilization; and days 16–28 post-immobilization recovery. Muscle biopsies were taken on d1, d8 (immobilization start), d15 (immobilization end), and d28 (post-immobilization recovery). Magnetic resonance imaging (MRI) was utilized to assess quadriceps muscle volume (Mvol), muscle cross-sectional area (CSA), and muscle fat-fraction (FF: the fraction of muscle occupied by fat). Maximal voluntary leg isometric torque was assessed by dynamometry. Administration of AXA2678 attenuated muscle disuse atrophy compared to PL (p < 0.05) with changes from d8 to d15 in PL: ΔMvol = −2.4 ± 2.3% and ΔCSA = −3.1% ± 2.1%, both p < 0.001 vs. zero; against AXA2678: ΔMvol: −0.7 ± 1.8% and ΔCSA: −0.7 ± 2.1%, both p > 0.3 vs. zero; and p < 0.05 between treatment conditions for CSA. During immobilization, muscle FF increased in PL but not in AXA2678 (PL: 12.8 ± 6.1%, AXA2678: 0.4 ± 3.1%; p < 0.05). Immobilization resulted in similar reductions in peak leg isometric torque and change in time-to-peak (TTP) torque in both groups. Recovery (d15–d28) of peak torque and TTP torque was also not different between groups, but showed a trend for better recovery in the AXA2678 group. Thrice daily consumption of AXA2678 for 28d was found to be safe and well-tolerated. Additionally, AXA2678 attenuated atrophy, and attenuated accumulation of fat during short-term disuse. Further investigations on the administration of AXA2678 in conditions of muscle disuse are warranted.Clinical Trial Registration: https://clinicaltrials.gov, identifier: NCT03267745.

Local Vibration Stimuli Induce Mechanical Stress-Induced Factors and Facilitate Recovery From Immobilization-Induced Oxidative Myofiber Atrophy in Rats.

Muscle atrophy can be caused by unloading stress such as microgravity environments or cast immobilization. Therapies for such disuse muscle atrophy and their underlying mechanisms are incompletely understood. Here, we investigated the therapeutic effects of local vibration stimulation on immobilization-induced skeletal muscle atrophy. A rat model was made by placing the left hindlimb in a cast for 1 week, leading to oxidative myofiber atrophy without myopathic changes in soleus skeletal muscle. Vibration stimulus (90 Hz, 15 min) to the plantar fascia of the atrophic hindlimb was performed once a day using a hand-held vibration massager after removal of a cast at the end of the immobilization period. After 2 weeks, rats were dissected, and quantitative analysis of the cross-sectional areas of soleus myofibers was performed. The results revealed that vibration induced significant recovery from disuse muscle atrophy, compared with untreated immobilized samples. Furthermore, vibration treatment suppressed the fiber transition from slow to fast fiber types compared with vibration-untreated immobilized samples. Western blotting analyses of mechanical stress-induced factors revealed that the expression of mechano-growth factor (MGF), systemic insulin-like growth factor I, and the mechanotransduction protein, Yes-associated protein 1 (YAP1), was decreased in untreated immobilized soleus muscle, whereas vibration stimulation restored their expression. No change in the level of phosphorylation of YAP1Ser127 was observed, leading to no change in p-YAP1/YAP1 ratio in vibration-treated immobilized soleus muscle. The results indicate that vibration stimulus is effective to restore immobilization-induced inactivation of YAP1 pathway. Phosphorylation of ERK 1/2, but not AKT, was enhanced in vibration-treated immobilized soleus muscle. Furthermore, vibration stimuli restored immobilization-induced downregulation of the paired box transcription factor, PAX7, a critical factor for regenerative myogenesis in muscle satellite cells. Our results indicate that cyclic vibration stimuli are effective in activating satellite cells and facilitate recovery from immobilization-induced oxidative myofiber atrophy through upregulation of MGF and YAP1.

A Comparative Histological and Immunohistochemical Study of the Effect of Oxandrolone and Whey Protein on Disuse Induced Muscle Atrophy in old aged male rats

Background: Periods of immobilization are often associated with pathologies and/or aging. These periods of disuse muscle atrophy could worsen the pathology or elderly frailty. Exercise, the best way to recover muscle mass, is not always applicable. Aim of Work: This study aimed to compare the therapeutic effect of oxandrolone versus whey protein on disuse induced muscle atrophy in old aged male rats with low testosterone level and mobility limitation.Materials and Methods: Twenty four aged male albino rats were included: 6 rats as control (group I). Eighteen rats were subjected to hind limb suspension (HLS) for 2 weeks then were divided into: 6 rats as group II (disuse atrophy) and 12 rats as group III (treated group) which was equally subdivided into: group IIIa (oxandrolone treated) and IIIb (whey protein treated) where oxandrolone 1.23 mg/kg and whey protein 9.25 gm/kg were given orally daily for 4 weeks. Rats were sacrificed after 6 weeks. Gastrocnemius muscle weight and total protein content were measured. Muscle specimens were stained with Hematoxylin and Eosin, PAS and immunohistochemical staining for Myogenin. Morphometric measurements of type I and type II fibers number and cross sectional area (CSA), number of myogenin positive cells (differentiated satellite cells) were taken and statistically analyzed. Results: Group II showed atrophic angulated muscle fibers and significant increase in type II fibers compared to the control. Subgroup IIIa showed muscle fibers with large diameter. Many rounded vesicular nuclei were observed among muscle fibers. A significant increase in type I fibers and number of myogenin positive cells as compared to the control and subgroup IIIb. Conclusion: Oxandrolone and whey protein treated subgroups showed improved muscle mass, CSA, total protein content, histological architecture of muscle fibers and increase of satellite cells number. However, oxandrolone showed better therapeutic potential in ameliorating disuse muscle atrophy.

Exercise preconditioning attenuates hind limb unloading-induced gastrocnemius muscle atrophy possibly via the HDAC4/Gadd45 axis in old rats.

The mechanisms involved in unloading-induced skeletal muscle loss may be age-specific, and the evidence for exercise preconditioning-induced protection against disuse muscle atrophy in aged rats is limited. Therefore, in this study, we investigated age-related differences in the activation of the HDAC4/Gadd45α pathway following hindlimb unloading (HU). We also assessed the protective effect of preconditioning exercise on this pathway in young and old rat gastrocnemius muscle. Three-month-old (young, n = 18) and 24-month-old (old, n = 18) male Wistar rats were assigned to the following groups: control group (n = 6), seven days of HU group (n = 6), and a bout of exercise preconditioning prior to HU (Ex+HU) group (n = 6). Rats of both ages in the Ex + HU group ran continuously on a motor-driven treadmill (0° slope, 20 m/min, 15 min) prior to HU. The gastrocnemius muscles were removed after 7 days of HU and analyzed for protein content and mRNA expression. Gastrocnemius muscle weight was significantly higher in the Ex+HU group than in the HU group of old rats, but not in young rats. Levels of HDAC4 protein and mRNA were significantly increased in the old HU group. However, the increase was significantly suppressed in the old Ex+HU group. Moreover, the protective effect of exercise preconditioning had a positive effect on Gadd45α mRNA and protein levels only in the old Ex+HU group. No exercise preconditioning-related protection was observed in the young rats. Our data indicated that a single bout of preconditioning exercise prior to HU may exert a protective effect in disuse muscle atrophy in old rats and that these effects may be partially mediated by the HDAC4/Gadd45α axis.

Intensive care unit–acquired weakness: unanswered questions and targets for future research

Intensive care unit–acquired weakness (ICU-AW) is the most common neuromuscular impairment in critically ill patients. We discuss critical aspects of ICU-AW that have not been completely defined or that are still under discussion. Critical illness polyneuropathy, myopathy, and muscle atrophy contribute in various proportions to ICU-AW. Diagnosis of ICU-AW is clinical and is based on Medical Research Council sum score and handgrip dynamometry for limb weakness and recognition of a patient’s ventilator dependency or difficult weaning from artificial ventilation for diaphragmatic weakness (DW). ICU-AW can be caused by a critical illness polyneuropathy, a critical illness myopathy, or muscle disuse atrophy, alone or in combination. Its diagnosis requires both clinical assessment of muscle strength and complete electrophysiological evaluation of peripheral nerves and muscles. The peroneal nerve test (PENT) is a quick simplified electrophysiological test with high sensitivity and good specificity that can be used instead of complete electrophysiological evaluation as a screening test in non-cooperative patients. DW, assessed by bilateral phrenic nerve magnetic stimulation or diaphragm ultrasound, can be an isolated event without concurrent limb muscle involvement. Therefore, it remains uncertain whether DW and limb weakness are different manifestations of the same syndrome or are two distinct entities. Delirium is often associated with ICU-AW but a clear correlation between these two entities requires further studies. Artificial nutrition may have an impact on ICU-AW, but no study has assessed the impact of nutrition on ICU-AW as the primary outcome. Early mobilization improves activity limitation at hospital discharge if it is started early in the ICU, but beneficial long-term effects are not established. Determinants of ICU-AW can be many and can interact with each other. Therefore, future studies assessing early mobilization should consider a holistic patient approach with consideration of all components that may lead to muscle weakness.

When Wolff's law isn't enough: training students to consider soft tissues in promoting skeletal health

The physiology of various organ systems has revealed extensive crosstalk among tissues such as adipose tissue, skeletal muscle, and bone. These findings have important implications for skeletal biology, particularly within the context of improving bone health during growth and with aging. The latter is especially significant for students in the health sciences, since the population over the age of 65 is the most rapidly growing demographic globally and in the United States. Mechanical loads emanating from body weight and muscle contraction are important for bone mass accrual early in life, but the response of bone to mechanical stimuli is markedly attenuated in adults. Though increased loading magnitude and frequency may have less dramatic anabolic effects on the adult skeleton than on young bones, inactivity and muscle disuse atrophy can contribute significantly to age‐related bone loss. This point is reinforced by data from clinical studies showing that older adults with low appendicular lean mass and reduced grip strength also have reduced cortical bone area and thickness. The highly integrated changes in skeletal muscle and bone observed in aging patient populations suggest that targeting either sarcopenia or osteoporosis alone may not be sufficient for effective fracture prevention. Thus, new strategies for improving both tissues simultaneously to prevent “osteosarcopenia” have been proposed. These recent advances underscore the importance of considering soft‐tissues for maintaining bone health and preventing falls and bone fractures.Support or Funding InformationNational Institute on Aging (AG 036675)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Role of astaxanthin supplementation in prevention of disuse muscle atrophy: a review

Role of astaxanthin supplementation in prevention of disuse muscle atrophy: a review

Influence of Gradual Loading on Disuse Atrophy of the Rat Soleus Muscle Depends on the Longitudinal Site

Influence of Gradual Loading on Disuse Atrophy of the Rat Soleus Muscle Depends on the Longitudinal Site

The Effects of Dokhwalgisaeng-tang against Disuse Muscle Atrophy in Gastrocnemius of Rats

Background: The purpose of this study was to examine the effect of Dokhwalgisaeng-tang on immobilization-induced muscle atrophy. Methods: Twenty young male Sprague-Dawley rats were divided into 2 groups. The rats in Dokhwalgisaeng-tang group were orally administered Dokhwalgisaeng-tang water extract, and the rats in the control group were given saline only. Hind limb immobilization was performed with casting tape to keep the left ankle joint in a fully extended position. No intervention was performed on the right leg which was used as an intact region. After 2 weeks of immobilization, all animals were sacrificed, and the gastrocnemius muscle was dissected from both legs and weighed. The morphology of the right and the left gastrocnemius muscle in both the Dokhwalgisaeng-tang and the control group was assessed by hematoxylin and eosin staining. The muscle cross sectional area was examined by image analysis (Axiovision LE software). In addition, immunohistochemical staining was carried out using the free-floating method, and the number of apoptotic related proteins were counted (anti-BAX, anti-Bcl-2). Results: Dokhwalgisaeng-tang showed a significant protective effect against the reduction of the left gastrocnemius muscle (weight and muscle cross sectional area) compared with the control group. Moreover, the treatment with Dokhwalgisaeng-tang significantly reduced protein expression of BAX and increased protein expression of Bcl-2 in the gastrocnemius muscle compared with the control group. Conclusion: Dokhwalgisaeng-tang showed protective effects against disuse muscle atrophy, potentially through altered BAX and Bcl-2 protein expression in the gastrocnemius muscle.

Ultralight Conductive and Elastic Aerogel for Skeletal Muscle Atrophy Regeneration

AbstractCell‐free materials that can transmit both mechanical and electrical stimulations provide a promising strategy for myoinjury repair. Skeletal muscle is sensitive to electrical stimulation (ES), and accordingly, materials are required to transmit the electrical signal while maintaining their elasticity to build the cellular communication network in denervated muscle for retarding muscle atrophy. Here, tannic acid functionalized with methacrylate group (TA–MA), dopamine, and hydrothermal reduction are employed in multistep base reduction to fabricate a polydopamine (PDA)/reduced graphite oxide (rGO) aerogel. This mussel‐inspired PDA/rGO aerogel possesses good conductivity, electromechanical stability, and appropriate Young's modulus, which are favorable for the growth and differentiation of C2C12 myoblasts. After the cell‐free PDA/rGO aerogel‐transplanted denervated muscle is loaded with cyclic ES for 3 weeks, the mean muscle fiber size increases by 90% and the maximum contraction force of denervated muscle elevates by 50%, accompanied with a slight inflammation infiltration in muscle. In conclusion, PDA/rGO aerogel is a safe and effective implant for retarding the disuse muscle atrophy.

Effect of a combination of astaxanthin supplementation, heat stress, and intermittent reloading on satellite cells during disuse muscle atrophy.

We examined the effect of a combination of astaxanthin (AX) supplementation, repeated heat stress, and intermittent reloading (IR) on satellite cells in unloaded rat soleus muscles. Forty-nine male Wistar rats (8-week-old) were divided into control, hind-limb unweighting (HU), IR during HU, IR with AX supplementation, IR with repeated heat stress (41.0-41.5 °C for 30 min), and IR with AX supplementation and repeated heat stress groups. After the experimental period, the antigravitational soleus muscle was analyzed using an immunohistochemical technique. Our results revealed that the combination of dietary AX supplementation and heat stress resulted in protection against disuse muscle atrophy in the soleus muscle. This protective effect may be partially due to a higher satellite cell number in the atrophied soleus muscle in the IR/AX/heat stress group compared with the numbers found in the other groups. We concluded that the combination treatment with dietary AX supplementation and repeated heat stress attenuates soleus muscle atrophy, in part by increasing the number of satellite cells.

Regulation of Protein Synthesis in Inactivated Skeletal Muscle: Signal Inputs, Protein Kinase Cascades, and Ribosome Biogenesis.

Disuse atrophy of skeletal muscles is characterized by a significant decrease in the mass and size of muscle fibers. Disuse atrophy develops as a result of prolonged reduction in the muscle functional activity caused by bed rest, limb immobilization, and real or simulated microgravity. Disuse atrophy is associated with the downregulation of protein biosynthesis and simultaneous activation of protein degradation. This review is focused on the key molecular mechanisms regulating the rate of protein synthesis in mammalian skeletal muscles during functional unloading.